Botulinum Toxin Suppression of CNS Network Activity In Vitro
The botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects o...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2014/732913 |
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| _version_ | 1832559088944283648 |
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| author | Joseph J. Pancrazio Kamakshi Gopal Edward W. Keefer Guenter W. Gross |
| author_facet | Joseph J. Pancrazio Kamakshi Gopal Edward W. Keefer Guenter W. Gross |
| author_sort | Joseph J. Pancrazio |
| collection | DOAJ |
| description | The botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects of BoNT. Murine spinal cord and frontal cortex networks cultured on substrate integrated microelectrode arrays allowed monitoring of spontaneous spike and burst activity with exposure to BoNT serotype A (BoNT-A). Exposure to BoNT-A inhibited spike activity in cultured neuronal networks where, after a delay due to toxin internalization, the rate of activity loss depended on toxin concentration. Over a 30 hr exposure to BoNT-A, the minimum concentration detected was 2 ng/mL, a level consistent with mouse lethality studies. A small proportion of spinal cord networks, but not frontal cortex networks, showed a transient increase in spike and burst activity with exposure to BoNT-A, an effect likely due to preferential inhibition of inhibitory synapses expressed in this tissue. Lastly, prior exposure to human-derived antisera containing neutralizing antibodies prevented BoNT-A induced inhibition of network spike activity. These observations suggest that the extracellular recording from cultured neuronal networks can be used to detect and quantify functional BoNT effects. |
| format | Article |
| id | doaj-art-98175d86a9ad4e7cb6c2e13359ad89f8 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-98175d86a9ad4e7cb6c2e13359ad89f82025-02-03T01:30:51ZengWileyJournal of Toxicology1687-81911687-82052014-01-01201410.1155/2014/732913732913Botulinum Toxin Suppression of CNS Network Activity In VitroJoseph J. Pancrazio0Kamakshi Gopal1Edward W. Keefer2Guenter W. Gross3Department of Bioengineering, George Mason University, 4400 University Drive, Fairfax, VA 22030, USADepartment of Speech and Hearing Sciences and CNNS, University of North Texas, Denton, TX 76203, USAPlexon Inc., Dallas, TX 75206, USADepartment of Biological Sciences and Center for Network Neuroscience (CNNS), University of North Texas, Denton, TX 76203, USAThe botulinum toxins are potent agents which disrupt synaptic transmission. While the standard method for BoNT detection and quantification is based on the mouse lethality assay, we have examined whether alterations in cultured neuronal network activity can be used to detect the functional effects of BoNT. Murine spinal cord and frontal cortex networks cultured on substrate integrated microelectrode arrays allowed monitoring of spontaneous spike and burst activity with exposure to BoNT serotype A (BoNT-A). Exposure to BoNT-A inhibited spike activity in cultured neuronal networks where, after a delay due to toxin internalization, the rate of activity loss depended on toxin concentration. Over a 30 hr exposure to BoNT-A, the minimum concentration detected was 2 ng/mL, a level consistent with mouse lethality studies. A small proportion of spinal cord networks, but not frontal cortex networks, showed a transient increase in spike and burst activity with exposure to BoNT-A, an effect likely due to preferential inhibition of inhibitory synapses expressed in this tissue. Lastly, prior exposure to human-derived antisera containing neutralizing antibodies prevented BoNT-A induced inhibition of network spike activity. These observations suggest that the extracellular recording from cultured neuronal networks can be used to detect and quantify functional BoNT effects.http://dx.doi.org/10.1155/2014/732913 |
| spellingShingle | Joseph J. Pancrazio Kamakshi Gopal Edward W. Keefer Guenter W. Gross Botulinum Toxin Suppression of CNS Network Activity In Vitro Journal of Toxicology |
| title | Botulinum Toxin Suppression of CNS Network Activity In Vitro |
| title_full | Botulinum Toxin Suppression of CNS Network Activity In Vitro |
| title_fullStr | Botulinum Toxin Suppression of CNS Network Activity In Vitro |
| title_full_unstemmed | Botulinum Toxin Suppression of CNS Network Activity In Vitro |
| title_short | Botulinum Toxin Suppression of CNS Network Activity In Vitro |
| title_sort | botulinum toxin suppression of cns network activity in vitro |
| url | http://dx.doi.org/10.1155/2014/732913 |
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